7. Project Summary/Abstract Problem: Throughout the world, lower respiratory infections cause significant death and mortality. Seasonal influenza pneumonia alone causes more than 40,000 deaths a year in the U.S. Pandemic influenzas have even more impacts, with at least 50 million influenza-related deaths in 1918-9. Further, the anticipated avian- origin H5N1 influenza in human populations with its associated high mortality is of great concern with no immediate solution currently available. Pulmotect's Solution: Pulmotect has identified and is developing a novel technology to prevent respiratory infections. The lead drug (PUL-042) is a combination of two TLR ligands that stimulates the lung's own innate defense mechanisms to create a hostile environment for pathogens and prevent or attenuate respiratory infections. Both in vitro and in vivo experiments have been completed to validate this technology and the drug is progressing through the regulatory process for a treatment to benefit cancer patients during periods of immunocompromise. The focus of this proposal is to accomplish key milestones that will further transition this technology for commercialization against viral infections. The project is organized into three measurable Specific Aims: This SBIR application is focused on addressing important preclinical important issues. The three Aims included are designed to validate and expand upon the proof-of-concept data already obtained. The Aims are focused for transitioning this technology into the clinic. Achieving these milestones would provide significant data for an IND application for a product that is safe and efficacious. Positive results from this phase I proposal would potentially lead to a phase II SBIR application to perform an in-depth study of the therapy in a second animal model, including FDA approved safety and toxicity studies. Additionally, by demonstrating subsequent discoveries in Pulmotect's pipeline, additional outside funds from investors can better be pursued to transition this technology into the clinic and market place. Overall, the outlined milestones of this proposal would build upon previous work, add to the foundation of this platform technology, and help bring this technology to the clinic.